Regioselective addition-elimination of Morita-Baylis-Hillman adducts with 2-naphthol or phenol catalyzed by functionalized ionic liquids: A direct strategy to construct functional alkenes

Article abstract of DOI:10.1139/cjc-2015-0358

A highly regioselective addition-elimination of Morita-Baylis-Hillman adducts promoted by base ionic liquids (0.5 mol%) was reported to afford a variety of functional alkenes in excellent yields (up to 99%). This protocol provides a new method to access functional alkenes directly. Recycled base ionic liquids could be reused at least five times and the isolated yield of the product was almost consistent after five runs.

Full text of DOI:10.1139/cjc-2015-0358

211
ARTICLE
Regioselective addition–elimination of Morita–Baylis–Hillman
adducts with 2-naphthol or phenol catalyzed by functionalized
ionic liquids: a direct strategy to construct functional alkenes
Chuan-Bao Zhang, Jun Zhang, Wei-Qiang Hu, Yan-Su Cui, Yong Liu, Ji-Ya Fu, and Tao Ding
Abstract: A highly regioselective addition–elimination of Morita–Baylis–Hillman adducts promoted by base ionic liquids
(0.5 mol%) was reported to afford a variety of functional alkenes in excellent yields (up to 99%). This protocol provides a new
method to access functional alkenes directly. Recycled base ionic liquids could be reused at least five times and the isolated yield
of the product was almost consistent after five runs.
Key words: Morita–Baylis–Hillman adducts, functional ionic liquids, addition–elimination, regioselective.
Résumé : Nous faisons état d’une réaction d’addition–élimination hautement régiosélective menée sur des adduits de Morita–
Baylis–Hillman, catalysée par des liquides ioniques (0,5 mol%) employés comme base et ayant produit une diversité d’alcènes
fonctionnels dans d’excellents rendements (jusqu’a` 99%). Le présent protocole offre une nouvelle méthode permettant d’accéder
directement aux alcènes fonctionnels. En outre, les liquides ioniques employés comme bases recyclables peuvent être réutilisées
au moins cinq fois; les rendements des produits isolés étant demeurés presque constants après cinq cycles. [Traduit par la
Rédaction]
Mots-clés : adduits de Morita–Baylis–Hillman, liquides ioniques fonctionnels, addition–élimination, régiosélective.
olution reagents, solvents, or catalysts.7 Up to the present, numerous
Introduction
FILs have been designed and successfully applied in promoting var-
Functional alkene-containing compounds widely exist in natu-
ious reactions.8 However, to the best of our knowledge, no FIL
ral products and pharmaceuticals of biological activities.1 Regiose-
catalysts have been used in the addition–elimination of MBH ad-
lective addition–elimination of Morita–Baylis–Hillman (MBH)
ducts, and it is still desirable to develop new efficient catalytic
adducts is one of the most efficient methods for functional alkene
systems for this reaction.
formation, which are potentially important building blocks for a
variety of valuable synthetic intermediates.2 MBH carbonates as
Results and discussion
synthetically useful synthons have attracted significant attention
from organic chemists.3
This work on the addition–elimination of MBH adducts with
2-naphthol showed that BILs were effective catalysts in this reac-
tion. Inspired by this interesting result, herein, we wish to report
our original work in the addition–elimination of MBH adducts
with 2-naphthol catalyzed by BILs in excellent yields and regiose-
lectivities (Chart 1).
Over the past years, great progress has been made in the addition–
elimination of MBH adducts. For the MBH adducts, the transfor-
mations of MBH carbonates have been directed toward the following
two sites: substitution of MBH carbonates at the ␤- or ␤=-position
with nucleophiles (Scheme 1).4 Substitution of MBH carbonates at
the ␤-position with nucleophiles has been well reported. 4 Substi-
tution of MBH carbonates at the ␤=-position with nucleophiles has
rarely been reported.5 In 2006, P.V. Ramachandran developed a
series of chiral phase-transfer catalysts for the direct substitution
of MBH carbonates at the ␤=-position in excellent yields and high
enantioselectivities.5c Subsequently, Y. Lu disclosed that quinidine-
derived tertiary aminethiourea catalyst promoted the substitution
of MBH carbonates at the ␤=-position with excellent yields and
enantioselectivities.5d Even though, the direct substitution of
MBH carbonates at the ␤=-position, especially 2-naphthol as nu-
cleophile, is still a challenge.
For further investigation on this addition–elimination reaction,
allylic carbonates (1a) and 2-naphthol (2a) were selected as model
reactants and the results are summarized in Table 1. A variety of
BIL catalysts 3a–3i were synthesized and tested in the model re-
action in CH3CN at 40 °C (Table 1, entries 1–8), and the anions of
the catalysts obviously affected the results. BIL catalysts 3e–3h
successfully gave 4a in moderate yields (60%–85%) (Table 1, en-
tries 5–8). Catalyst 3e gave the best yield (85%) (Table 1, entry 5).
To further optimize the reaction conditions, a series of solvents
were investigated in the presence of 20 mol% 3e and the results
are presented in Table 1 (entries 10–17). All solvents gave moderate
to good yields (57%–99%) except dichloromethane (DCM). When
MeOH was used, 57% yield was obtained (Table 1, entry 12). Dimeth-
yl sulfoxide (DMSO) delivered the highest yield (99%) at 40 °C
(Table 1, entry 16). Based on these results, DMSO was chosen as a
candidate solvent for further screenings (Table 1, entry 17).
Functionalized ionic liquids (FILs) are receiving growing atten-
tion in the fields of catalysis due to their unique structures, phys-
ical and chemical properties, and green credentials as reusable
catalysts.6 Recently, base ionic liquids (BILs) have emerged as an
important type of functionalized ionic liquids and applied as res-
Received 24 July 2015. Accepted 21 September 2015.
C.-B. Zhang, J. Zhang, W.-Q. Hu, Y.-S. Cui, Y. Liu, J.-Y. Fu, and T. Ding. College of Chemistry and Chemical Engineering, Henan University, Institute
of Fine Chemistry and Engineering, Henan Engineering Laboratory of Flame-Retardant and Functional Materials, Kaifeng, Henan 475004, P. R. China.
Corresponding authors: Ji-Ya Fu (email: fujiya@126.com) and Tao Ding (email: dingtao@henu.edu.cn).
Can. J. Chem. 94: 211–214 (2016) dx.doi.org/10.1139/cjc-2015-0358
Published at www.nrcresearchpress.com/cjc on 25 November 2015.

212
Can. J. Chem. Vol. 94, 2016
Scheme 1. Substitution of MBH carbonates with pronucleophiles.
Chart 1. Reaction of allylic carbonates (1a) and 2-naphthol (2a).
To further improve the yields, other parameters such as catalyst
loading, amount of MBH adducts, and temperature were also stud-
ied. The catalyst loading was also examined in DMSO at 40 °C and
the results are described in Table 1 (entries 18–22). Catalyst loading
exerted a slight influence on the yields. Lowering catalyst loading
to 0.5 mol%, high yields were obtained (89%) (Table 1, entry 22).
Further examinations showed that increasing the molar ratio of
MBH adducts had no obvious change in yields (Table 1, entry 23).
Decreasing the amount of MBH adducts significantly affected the
yields (Table 1, entry 24). Continually, reaction temperature was
studied. Lowering the temperature to 25 °C increased obviously
the yields (98% yield) (Table 1, entry 25 versus 22). Thus, through
those screenings, the optimized reaction conditions were found
to be a reaction of 1.2 equiv. of 1a with 1.0 equiv. of 2a in the
presence of 0.5 mol% of 3e in DMSO at 25 °C (Table 1, entry 25).
Under optimized conditions, various MBH adducts (1) and 2-naphthol
(2a) were evaluated (Chart 2) and the results are summarized in
Table 2. Generally, all the cases proceeded smoothly and afforded
the corresponding adducts 4 with moderate to excellent yields
(59%–99%). Good results were obtained for different substituents
on the phenyl of MBH adducts (Table 2, entries 1–14). Substituents
on the 4-position of the phenyl group exerted obvious effects on
the reactivities, and an obvious variety of yields were observed.
Both electron-withdrawing and electron-donating substituents af-
forded lower yields (59%–73%) (Table 2, entries 3, 4, and 6–8) except
4-chlorophenyl-substituted MBH adducts (95%) (Table 2, entry 5). The
position of the substituents was also tested. The yields were obvi-
ously sensitive to the position of the substituents on the aromatic
of MBH adducts, although the para substituents gave higher yields
compared with the corresponding meta- and ortho-substituted
counterparts (Table 2, entries 5, 9 versus 13). 1-NaphthylMBH
adducts gave an excellent yield (99%) (Table 2, entry 14). When
the reaction was carried out on a multigram scale, a high yield was
still obtained (92%) (Table 2, entry 2).
The addition–elimination of MBH adducts with phenol was also
investigated (Table 2, entries 15–19). This catalytic system was still
effective for phenol and 85%–99% yields were achieved. These results
indicated that BIL 3e was efficient for the addition–elimination of
MBH adducts with 2-naphthol or phenol.
The reusability of ionic liquids is the key factor that identifies
whether it finds a potential application in industry. To test the
catalyst reusability and convenience of recycling, the reaction was
Published by NRC Research Press

Zhang et al.
213
Table 1. Screening of catalysts and optimized conditions for
Table 2. Scope of substrates.
the reaction of allylic carbonates (1a) and 2-naphthol (2a).
Entry
R-group
2
Time (h)
Yield (%)a
Catalyst
loading
(%)
1
Ph (1a)
Ph (1a)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
17
20
138
23
45
23
138
52
138
23
24
138
137
23
6
98 (4a)
92 (4a)
59 (4b)
68 (4c)
95 (4d)
73 (4e)
71 (4f)
67 (4g)
83 (4h)
69 (4i)
88 (4i)
99 (4j)
90 (4k)
99 (4l)
89 (4m)
90 (4n)
85 (4o)
93 (4p)
99 (4q)
Time
(h)
Yield
(%)a
2b
3
Entry
Catalyst
Solvent
p-NO2C6H4 (1b)
p-FC6H4 (1c)
p-ClC6H4 (1d)
p-BrC6H4 (1e)
p-CH3C6H4 (1f)
p-CH3OC6H4 (1g)
o-ClC6H4 (1h)
o-BrC6H4 (1i)
o-BrC6H4 (1i)
o-CH3C6H4 (1j)
m-ClC6H4 (1k)
1-naphthyl (1l)
1a
4
5
6
7
8
9
10
11c
12
13
14
15
16
17
18
19
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCM
Et2O
MeOH
EtOH
THF
DMF
DMSO
Toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
10
5
69
69
69
69
69
69
69
69
69
192
192
192
192
192
3
2.5
192
4
4
5
15
15
20
20
17
n.r.
n.r.
n.r.
n.r.
85
81
84
60
29
Trace
88
57
84
81
83
99
Trace
97
96
3g
3h
DABCO
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
3e
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23b
24c
25d
1f
1i
1j
1l
18
1
1
18
Note: Unless otherwise specified, all reactions were carried out
with 1 (0.18 mmol), 2a (0.15 mmol), and catalyst 3e (0.5 mol%) in DMSO
(1.0 mL) at 25 °C.
aIsolated yield.
2
1
0.5
0.5
0.5
0.5
96
94
89
89
73
98
bCarried out with 1a (4.5 mmol), 2a (3.75 mmol), and catalyst 3e
(0.5 mol%) in DMSO (25 mL) at 25 °C.
cCarried out with 1i (0.18 mmol), 2a (0.15 mmol), and catalyst 3e
(20 mol%) in DMSO (1.0 mL) at 25 °C.
Fig. 1. Recyclability of the catalyst. Reaction conditions:
Note: Unless otherwise specified, all reactions were carried out
with 1a (0.18 mmol), 2a (0.15 mmol), and catalyst 3 (20 mol%) in
solvent (1.0 mL) at 40 °C.
1i (0.18 mmol), 2a (0.15 mmol), catalyst 3e (20 mol%), t = 24 h, 25 °C.
aIsolated yield; n.r., no reaction.
bCarried out by using 0.225 mmol of 1a and 0.15 mmol of 2a.
cCarried out by using 0.15 mmol of 1a and 0.15 mmol of 2a.
dCarried out at 25 °C.
Chart 2. Scope of substrates for the reaction of allylic carbonates (1)
and 2-naphthol (2) under optimized conditions.
Supplementary material
carried out in the presence of a catalytic amount of BIL 3e under
the conditions with 1i (0.18 mmol), 2a (0.15 mmol), and catalyst 3e
(20 mol%), and t = 24 h at 25 °C. When the reaction was completed,
the reaction mixture was concentrated in vacuo and extracted
with DCM and the ionic liquid left in the aqueous phase was
concentrated in vacuo. Recycled BIL 3e was directly used in the
next run and the results indicated that the isolated yield of the
product 4i was almost consistent after five runs and 3e could be
reused at least five times (Fig. 1).
Supplementary material is available with the article through the
journal Web site at http://nrcresearchpress.com/doi/suppl/10.1139/
cjc-2015-0358.
Acknowledgements
This work was supported by the Science and Technology Devel-
opment Project of Henan Province (No. 134300510072) and the
National Natural Science Foundation of China (No. 21206031).
References
Conclusion
(1) (a) Shanmugam, P.; Vaithiyanathan, V. Tetrahedron 2008, 64, 3322. doi:10.
1016/j.tet.2008.02.002; (b) Zhang, P. Z.; Gu, J.; Zhang, G. L. J. Asian Nat. Prod.
Res. 2015, 17, 217. doi:10.1080/10286020.2015.1006202; (c) Hikosaka, G.;
Hattori, Y.; Makabe, H. Tetrahedron 2014, 25, 1367. doi:10.1016/j.tetasy.2014.
08.008.
In summary, we have successfully demonstrated the regioselec-
tive addition–elimination of MBH adducts with 2-naphthol or
phenol in excellent yields (up to 99%) efficiently promoted by
environmental friendly FILs (0.5 mol%). This work provided an
effective method for the construction of functional alkene com-
pounds. Further applications of this transformation and new phar-
maceutical preparations are currently underway in our laboratory.
(2) Selected examples: (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev.
2003, 103, 811. doi:10.1021/cr010043d; (b) Declerck, V.; Martinez, J.;
Lamaty, F. Chem. Rev. 2009, 109, 1. doi:10.1021/cr068057c; (c) Singh, V.;
Batra, S. Tetrahedron 2008, 64, 4511. doi:10.1016/j.tet.2008.02.087; (d) Masson, G.;
Housseman, C.; Zhu, J. Angew. Chem. Int. Ed. 2007, 46, 4614. doi:10.1002/anie.
Published by NRC Research Press

214
Can. J. Chem. Vol. 94, 2016
200604366; (e) Shi, Y.-L.; Shi, M. Eur. J. Org. Chem. 2007, 2905. doi:10.1002/
ejoc.200700030; (f) Ma, G.-N.; Jiang, J.-J.; Shi, M.; Wei, Y. Chem. Commun. 2009,
5496. doi:10.1039/b909405a.
2000, 122, 3534. doi:10.1021/ja994326n; (b) Roy, S. J. S.; Mukherjee, S. Chem.
Commun. 2014, 50, 121. doi:10.1039/C3CC47645F; (c) Ramachandran, P. V.;
Madhi, S.; Bland-Berry, L.; Reddy, M. V. R.; O’Donnel, M. J. J. Am. Chem. Soc.
2005, 127, 13450. doi:10.1021/ja052638m; (d) Chen, G.-Y.; Zhong, F.; Lu, Y. Org.
Lett. 2011, 13, 6070. doi:10.1021/ol202555v; (e) Badkar, P. A; Rath, N. P.;
Spilling, C. D. Org. Lett. 2007, 9, 3619. doi:10.1021/ol701500s; (f) Chen, C.-G.;
Hou, X.-L.; Pu, L. Org. Lett. 2009, 11, 2073. doi:10.1021/ol900439h.
(6) Selected examples: (a) Wasserscheid, P.; Keim, W. Angew. Chem. Int. Ed.
2000, 39, 3772. doi:10.1002/1521-3773(20001103)39:21<3772::AID-ANIE3
772>3.0.CO;2-5; (b) Welton, T. Chem. Rev. 1999, 99, 2071. doi:10.1021/
cr980032t; (c) Wilkes, J. S. Green Chem. 2002, 4, 73. doi:10.1039/b110838g.
(7) Selected examples: (a) Mi, X.; Luo, S.; Cheng, J.-P. J. Org. Chem. 2005, 70, 2338.
doi:10.1021/jo048391d; (b) Langer, P. Angew. Chem. Int. Ed. 2000, 39, 3049.
doi:10.1002/1521-3773(20000901)39:17<3049::AID-ANIE3049>3.0.CO;2-5;
(c) Mi, X. L.; Luo, S. Z.; He, J. Q.; Cheng, J.-P. Tetrahedron Lett. 2004, 45, 4567.
doi:10.1016/j.tetlet.2004.04.039; (d) Sheldon, R. Chem. Commun. 2001, 2399.
doi:10.1039/b107270f.
(3) Selected example: Deng, H.-P.; Wei, Y.; Shi, M. Org. Lett. 2011, 13, 3348.
doi:10.1021/ol201094f.
(4) Selected examples: (a) Furukawa, T.; Nishimine, T.; Tokunaga, E.;
Hasegawa, K.; Shiro, M.; Shibata, N. Org. Lett. 2011, 13, 3972. doi:10.1021/
ol201490e; (b) Deng, H.-P.; Wei, Y.; Shi, M. Eur. J. Org. Chem. 2011, 1956.
doi:10.1002/ejoc.201001660; (c) Pei, C.-K.; Zhang, X.-C.; Shi, M. Eur. J. Org.
Chem. 2011, 4479. doi:10.1002/ejoc.201100501; (d) Yang, W.; Wei, X.; Pan, Y.;
Lee, R.; Zhu, B.; Liu, H.; Yan, L.; Huang, K.-W.; Jiang, Z.; Tan, C.-H.
Chem. Eur. J. 2011, 17, 8066. doi:10.1002/chem.201100929; (e) Hon, L.;
Sun, W.; Liu, C.; Zhao, D.; Wang, R. Chem. Commun. 2010, 46, 2856. doi:10.
1039/b926037d; (f) Huang, J.-R.; Cui, H.-L.; Lei, J.; Sun, X.-H.; Chen, Y.-C. Chem.
Commun. 2011, 47, 4784. doi:10.1039/C0CC05616B; (g) Yang, Y.-L.; Pei, C.-K.;
Shi, M. Org. Biomol. Chem. 2011, 9, 3349. doi:10.1039/C1OB00017A; (h) Jiang, Y.-Q.;
Shi, Y.-L.; Shi, M. J. Am. Chem. Soc. 2008, 130, 7202. doi:10.1021/ja802422d;
(i) Kamlar, M.; Hybelbauerová, S.; Císarˇová, I.; Veselý, J. Org. Biomol. Chem.
2014, 12, 5071. doi:10.1039/c4ob00682h; (j) Sun, W.; Hong, L.; Liu, C.;
Wang, R. Org. Lett. 2010, 12, 3914. doi:10.1021/ol101601d; (k) Liu, T.-Y.; Xie, M.;
Chen, Y.-C. Chem. Soc. Rev. 2012, 41, 4101. doi:10.1039/c2cs35017c.
(8) Selected examples: (a) Rosa, J. N.; Afonso, C. A. M.; Santos, A. G. Tetrahedron
2001, 57, 4189. doi:10.1016/S0040-4020(01)00316-7; (b) Hsu, J.-C.; Yen, Y.-H.;
Chu, Y.-H. B. Tetrahedron Lett. 2004, 45, 4673. doi:10.1016/j.tetlet.2004.04.099;
(c) Kim, E. J.; Ko, S. Y. Helv. Chim. Acta 2003, 86, 894. doi:10.1002/hlca.
200390087.
(5) Selected examples: (a) Trost, B. M.; Tsui, H.-C.; Toste, F. D. J. Am. Chem. Soc.
Published by NRC Research Press